Background: Increasing experimental evidence supports the concept that the RAAS (renin-angiotensin-aldosterone system) is involved in the pathogenesis of intracranial aneurysm rupture. However, it is still unclear whether RAAS inhibitors could reduce the risk of rupture of intracranial aneurysms. Methods: We performed a chart review of a prospectively maintained multicenter database of 3044 hypertensive patients with intracranial aneurysms from 20 medical centers in China. Patients were separated into broken and unbroken groups. Univariable and multivariable logistic regression analyzes were performed to determine the association between RAAS inhibitor use and risk of rupture. Sensitivity analyzes and subgroup analyzes were performed to verify the robustness of the results. Results: In multivariable analysis, female sex, passive smoking, uncontrolled or unmonitored hypertension, use of more than 2 antihypertensive medications, use of RAAS inhibitors, use of antihyperglycemic agents, hyperlipidemia, ischemic stroke, and aneurysm location were independently associated with risk of rupture. Use of RAAS inhibitors was significantly associated with a reduced risk of rupture compared with use of non-RAAS inhibitors (odds ratio, 0.490 [95% CI, 0.402–0.597]; P=0.000). Compared with the use of non-RASA inhibitors, the use of ACE (angiotensin-converting enzyme) inhibitors (odds ratio, 0.559 [95% CI, 0.442–0.709]; P=0.000), and the use of ARBs angiotensin receptors; odds ratio, 0.414 [95% CI, 0.315–0.542]; P = 0.000) were significantly associated with a reduced risk of rupture . The negative association of rupture risk with RAAS inhibitors was consistent in all 3 analyzed data and predefined subgroups (including controlled hypertension). Conclusions: RAAS inhibitor use was significantly associated with a lower risk of rupture independent of blood pressure control among hypertensive patients with intracranial aneurysms. |
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A multicenter study of more than 3,000 people with high blood pressure and brain aneurysms found that using RAAS inhibitors, a class of blood pressure-lowering medications, reduced the risk of aneurysm rupture by 18%, according to a new study. research published in Hypertension, a peer-reviewed journal of the American Heart Association .
An aneurysm is a bulge or weakening in the wall of an artery. When this happens in an artery of the brain, it is called an intracranial aneurysm. If an intracranial aneurysm ruptures, it spills blood around the brain and cuts off oxygen to the affected area, which can cause a hemorrhagic stroke, coma, and death. These strokes account for 3-5% of all strokes, but a higher proportion of morbidity and mortality than other types of stroke.
Each year, approximately 30,000 adults in the United States have intracranial aneurysms that rupture, according to the National Institute of Neurological Disorders and Stroke. Additionally, stroke is a leading cause of disability in the United States.
The renin-angiotensin-aldosterone system (RAAS) includes hormones that affect blood pressure regulation, and dysregulation of the RAAS can lead to the development of high blood pressure. Two components of RAAS have been shown to be involved in the development of intracranial aneurysms, and previous research has found that deregulation of RAAS may also contribute to aneurysm rupture. RAAS inhibitors, medications that block the effects of RAAS, are often used to treat high blood pressure.
"About half of patients with intracranial aneurysms have high blood pressure, which can cause vascular inflammation and increase the risk of aneurysm rupture," said the study’s senior author, Qinghai Huang, M.D., Ph.D., professor of neurosurgery at Changhai Hospital, Second Military Medical University in Shanghai, China. "Given that one-third of patients with ruptured aneurysms die and another third remain dependent for activities of daily living, it is necessary to identify modifiable risk factors to prevent aneurysm rupture."
This multicenter study analyzed data collected between 2016 and 2021 at 20 medical centers in different regions of China, collected before and after rupture, to evaluate the association between the use of RAAS inhibitors and other blood pressure medications, including beta blockers. and diuretics, on the risk of aneurysm rupture.
More than 3,000 adults with high blood pressure and intracranial aneurysms were included . The study sample was one-third men and two-thirds women, with an average age of 61 years. Participants’ hypertension status was classified as controlled (normal blood pressure with the use of antihypertensive medications) or uncontrolled (high blood pressure, defined as 140/90 or higher, with the use of antihypertensive medications), and was determined by Blood pressure measurements taken at one point, three months before they were hospitalized for an aneurysm.
The analysis found that 32% of participants who took RAAS inhibitors experienced an intracranial aneurysm rupture, compared with 67% of those who did not use RAAS inhibitors.
“We were surprised to find that, even among people with controlled hypertension , those who took RAAS inhibitors still had a significantly lower risk of rupture than people who did not use RAAS inhibitors. “Our study highlights that using appropriate antihypertensive medications to achieve normalization of blood pressure can markedly decrease the risk of aneurysm rupture,” Huang said.
“Based on these data, we estimate that almost 18% of ruptured aneurysms can be prevented if all patients with high blood pressure and intracranial aneurysms are prescribed RAAS inhibitors. "Because of the strong potential benefit and high safety of RAAS inhibitors, these findings may also help doctors optimize treatment to help people with high blood pressure prevent aneurysm rupture."
Using a multivariable model, the researchers estimated that women ’s risk of aneurysm rupture was 1.8 times greater than men’s risk, and that the following factors increased the risk of aneurysm rupture:
- Uncontrolled hypertension.
- Exposure to secondhand smoke.
- Untreated type 2 diabetes.
“These findings confirm previous studies indicating that, in addition to blood pressure control, smoking cessation and aggressive treatment of type 2 diabetes may also help reduce the risk of aneurysm rupture,” Huang said. "However, more research is needed to understand how RAAS inhibitors are involved in preventing intracranial aneurysm rupture in adults with high blood pressure."
The authors noted that limitations include the retrospective nature of the study, the existence of potential confounding factors, that hypertension was defined as a blood pressure of 140/90, rather than 130/80, that the exact value of blood pressure of the participants and that the duration and dose of RAAS inhibitors were not recorded in the database.
Co-authors are Ping Zhong, MD; Zhiwen Lu, MD; Zhangyu Li, MD; Tianxiao Li, M.D., Ph.D.; Qing Lan, M.D., Ph.D.; Jianmin Liu, M.D., Ph.D.; Zhanxiang Wang, M.D., Ph.D.; and Sifang Chen, M.D., Ph.D. Author statements are found in the manuscript.
This study was funded by the National Key Chronic Diseases Research and Development Project, Fujian Provincial Natural Science Foundation of China) and the Medical Project of Xiamen Municipal Science and Technology Bureau.
